Data obtained from research done with HIV-1 infected people supports the hypothesis that potent cellular immune response contribute to the control of HIV-1. This is especially true for long-term survivors. However, this type of data is only be viewed circumstantial evidence and definitive experiments to document the role of cellular immunity cannot be done in humans. We therefore propose to use adjuvant-active nonionic block copolymers in subunit vaccine formulations to induce in rhesus macaques, cellular immune responses with properties similar to the Th1 and Th2 responses defined in mice. In the first experiment, macaques will be vaccinated and the immune responses thoroughly characterized before the animals are infected with a pathogenic chimeric simian/human immunodeficiency virus (SHIV). The primary goal is to identify correlates of protective immunity for HIV-1 related viruses. A secondary goal is to determine which type of cellular immune responses may contribute to pathogenesis and potentially enhance disease. In the second and third experiments, animals will be infected prior to vaccination to determine the utility of selected vaccine formulations for augmenting immune responses after infection. The goal here is to identify immune responses that may contribute in a therapeutic manner. These studies will also allow for the identification one or more adjuvant-active copolymers for potential use in human prophylactic and therapeutic HIV-1 vaccines.
